Qiao Zheng, Xu Jingli, Fisher Darrell R, Gonzalez Rene, Miao Yubin
Department of Radiology, University of Colorado Denver, Aurora, CO 80045, USA.
Versant Medical Physics and Radiation Safety, Richland, WA 99354, USA.
Cancers (Basel). 2023 May 14;15(10):2755. doi: 10.3390/cancers15102755.
The aim of this study was to evaluate the effect of linker on tumor targeting and biodistribution of Cu-NOTA-PEGNle-CycMSH {Cu-1,4,7-triazacyclononane-1,4,7-triyl-triacetic acid-polyethylene glycol-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-CONH} and Cu-NOTA-GGNle-CycMSH {Cu-NOTA-GlyGlyNle-CycMSH} on melanoma-bearing mice. NOTA-PEGNle-CycMSH and NOTA-GGNle-CycMSH were synthesized and purified by HPLC. The biodistribution of Cu-NOTA-PEGNle-CycMSH and Cu-NOTA-GGNle-CycMSH was determined in B16/F10 melanoma-bearing C57 mice. The melanoma imaging property of Cu-NOTA-PEGNle-CycMSH was further examined in B16/F10 melanoma-bearing C57 mice. Cu-NOTA-PEGNle-CycMSH exhibited higher tumor uptake than Cu-NOTA-GGNle-CycMSH at 2, 4, and 24 h post-injection. The tumor uptake of Cu-NOTA-PEGNle-CycMSH was 27.97 ± 1.98, 24.10 ± 1.83, and 9.13 ± 1.66% ID/g at 2, 4, and 24 h post-injection, respectively. Normal organ uptake of Cu-NOTA-PEGNle-CycMSH was lower than 2.6% ID/g at 4 h post-injection, except for kidney uptake. The renal uptake of Cu-NOTA-PEGNle-CycMSH was 6.43 ± 1.31, 2.60 ± 0.79, and 0.90 ± 0.18% ID/g at 2, 4, and 24 h post-injection, respectively. Cu-NOTA-PEGNle-CycMSH showed high tumor to normal organ uptake ratios after 2 h post-injection. The B16/F10 melanoma lesions could be clearly visualized by single photon emission computed tomography (SPECT) using Cu-NOTA-PEGNle-CycMSH as an imaging probe at 4 h post-injection. The favorable tumor targeting and biodistribution properties of Cu-NOTA-PEGNle-CycMSH underscored its potential as an MC1R-targeted therapeutic peptide for melanoma treatment.
本研究的目的是评估连接基对Cu-NOTA-PEGNle-CycMSH{Cu-1,4,7-三氮杂环壬烷-1,4,7-三基-三乙酸-聚乙二醇-Nle-c[天冬氨酸-组氨酸-二苯丙氨酸-精氨酸-色氨酸-赖氨酸]-CONH}和Cu-NOTA-GGNle-CycMSH{Cu-NOTA-甘氨酰甘氨酰-Nle-CycMSH}在荷黑素瘤小鼠体内的肿瘤靶向性和生物分布的影响。NOTA-PEGNle-CycMSH和NOTA-GGNle-CycMSH通过高效液相色谱法合成并纯化。在荷B16/F10黑素瘤的C57小鼠中测定了Cu-NOTA-PEGNle-CycMSH和Cu-NOTA-GGNle-CycMSH的生物分布。在荷B16/F10黑素瘤的C57小鼠中进一步研究了Cu-NOTA-PEGNle-CycMSH的黑素瘤成像特性。注射后2、4和24小时，Cu-NOTA-PEGNle-CycMSH的肿瘤摄取高于Cu-NOTA-GGNle-CycMSH。注射后2、4和24小时，Cu-NOTA-PEGNle-CycMSH的肿瘤摄取分别为27.97±1.98、24.10±1.83和9.13±1.66%ID/g。注射后4小时，Cu-NOTA-PEGNle-CycMSH在正常器官的摄取低于2.6%ID/g，但肾脏摄取除外。注射后2、4和24小时，Cu-NOTA-PEGNle-CycMSH在肾脏的摄取分别为6.43±1.31、2.60±0.79和0.90±0.18%ID/g。注射后2小时，Cu-NOTA-PEGNle-CycMSH显示出高的肿瘤与正常器官摄取比。注射后4小时，使用Cu-NOTA-PEGNle-CycMSH作为成像探针，通过单光子发射计算机断层扫描（SPECT）可以清晰地观察到B16/F10黑素瘤病变。Cu-NOTA-PEGNle-CycMSH良好的肿瘤靶向性和生物分布特性突出了其作为靶向MC1R的治疗性肽用于黑素瘤治疗的潜力。
